Rh(II)-catalyzed intramolecular annulation of N-sulfonyl 1,2,3-triazoles with indole derivatives: A new method for synthesis pyranoindoles

Article abstract of DOI:10.1016/j.tet.2016.04.017

A direct and highly stereoselective approach for the synthesis of Z-alkenyl-pyranoindoles had been developed by utilizing Rh(II)-catalyzed intramolecular cyclization of N-sulfonyl-1,2,3-triazoles with indole derivatives. A variety of pyranoindoles were obtained in 44-93% yields. Moreover, a more convenient synthesis of pyranoindoles starting from terminal alkyne was realized via a Cu-Rh sequentially catalyzed one-pot cascade reaction.

Full text of DOI:10.1016/j.tet.2016.04.017

Accepted Manuscript
Rh(II)-catalyzed intramolecular annulation of N-sulfonyl 1,2,3-triazoles with indole
derivatives: A new method for synthesis pyranoindoles
Hui Xie, Jian-Xin Yang, Pranjal Protim Bora, Qiang Kang
PII:
S0040-4020(16)30270-8
10.1016/j.tet.2016.04.017
TET 27660
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 22 February 2016
Revised Date: 1 April 2016
Accepted Date: 6 April 2016
Please cite this article as: Xie H, Yang J-X, Bora PP, Kang Q, Rh(II)-catalyzed intramolecular annulation
of N-sulfonyl 1,2,3-triazoles with indole derivatives: A new method for synthesis pyranoindoles,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.04.017.
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ACCEPTED MANUSCRIPT
Rh(II)-catalyzed intramolecular annulation of N-sulfonyl
1,2,3-triazoles with indole derivatives: A new method for synthesis
pyranoindoles
Hui Xie,a Jian-Xin Yang,a Pranjal Protim Bora b and Qiang Kang*b
a Hainan Provincial Fine Chemical Engineering Research Center, Hainan University,
Haikou, Hainan 570228, China.
b Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian
Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155
Yangqiao Road West, Fuzhou, 350002, China.
* Corresponding author. Tel.: (+86) 591-63173548 ; fax: (+86) 591-63173548; e-mail
address: kangq@fjirsm.ac.cn
Abstract: A direct and highly stereoselective approach for the synthesis of
Z-alkenyl-pyranoindoles had been developed by utilizing Rh(II)-catalyzed
intramolecular cyclization of N-sulfonyl-1,2,3-triazoles with indole derivatives. A
variety of pyranoindoles were obtained in 44 - 93% yields. Moreover, a more
convenient synthesis of pyranoindoles starting from terminal alkyne was realized via
a Cu-Rh sequentially catalyzed one-pot cascade reaction.
R3O2S
R3O2S
N
N
NH
N
R1
O
R1
2 mol% Rh2(Oct)4
O
toluene, 100 oC,
10 - 90 min
N
N
R2
R2
upto 93% yield
# High stereoselectivity
# One-pot synthesis from terminal alkyne
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Keywords: sulfonyl triazoles, α-imino Rh(II) carbenes, Rh(II)-catalyzed,
pyranoindoles, alkyne.
1. Introduction
Pyranoindole is an important structural motif, molecules comprising the
pyranoindole framework are known to exhibit interesting biological activities.
Etodolac1 and pemedolac2 bearing tetrahydropyrano[3,4-b]indole skeleton are
anti-inflammatory and analgesic agents whereas some others are potent inhibitors of
hepatitis C virus (HCV) NS5B polymerase3 (Fig 1).
Fig. 1. Bioactive compounds bearing pyranoindole skeleton.
Due to their interesting pharmacological properties, pyranoindoles have received
considerable attention and multiple synthetic routes towards this class of compounds
have been developed.4 Zhang and coworkers5 demonstrated a silicon-directed
oxa-Pictet-Spengler cyclizations of 2-(2-trimethylsilanyl-1H-indol-3-yl)-ethanols with
various ketones and aldehydes for the synthesis of tetrahydro-pyrano-[3,4-b]indoles
(eqn. a, Scheme 1). Likewise, Gharpure and Prasath explored oxa-Pictet–Spengler
type reaction of vinylogous carbonates for stereoselective synthesis of pyranoindoles.6
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Nielsen and co-workers had also demonstrated a ruthenium hydride/Brønsted
acid-catalyzed tandem sequence towards the synthesis of pyranoindoles (eqn. b,
Scheme 1).7 In another interesting example, Porco Jr. group realized a Friedel-Crafts
alkylation approach for the synthesis of pyrano-[3,4-b]indoles containing an
uncommon C3-C4 substitution pattern.8 Very recently, Asensio and co-workers
reported an efficient synthesis of pyranoindoles via gold(I)-catalyzed intramolecular
hydroaminative/arylative cascade (eqn. c, Scheme 1).9 Recently, generation of
α-imino Rh(II) carbenes from readily accessible N-sulfonyl-1,2,3-triazole and their
reactions have enjoyed a great deal of popularity among the synthetic chemistry
community.10 The N-sulfonyl-1,2,3-triazole derived Rh(II) carbenes have been widely
employed for the synthesis of N-heterocycles,11 stereoselective cycloadditions,12 C-H
bond insertion,11o,11p,13 X-H bond insertion (X = heteroatoms),14 and other
transformations15. In continuation of our effort on synthesis of biologically relevant
heterocycles utilizing N-sulfonyl-1,2,3 triazoles,16 herein we report Rh(II)-catalyzed
intramolecular annulation of N-sulfonyl-1,2,3-triazoles towards highly stereoselective
synthesis of pyranoindoles (eqn. d, Scheme 1).
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Scheme 1. Synthesis of pyranoindoles
2. Results and discussion
We began our initial investigation of Rh(II)-catalyzed intramolecular annulation,
taking indolyl triazole, 1a
by
(2-(((1-(methylsulfonyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)-1H-indole) as model
substrate. The reaction of 0.1 M solution of 1a in dichloromethane in the presence of
2 mol% [Rh2(Oct)4] at 30 oC resulted the exclusive Z-isomer 2a in 30% isolated yield,
which was unambiguously confirmed by single crystal X-ray diffraction analysis17
(Table 1, entry 1). The model reaction in dichloroethane under similar conditions
didn’t show significant improvement (Table1, entry 2). However, when it was carried
o
out in toluene at 30 C, the isolated yield of desired 2a was improved to 51%. Since
o
sulfonyl triazole 1a is only partially soluble in toluene at 30 C, the reaction
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o
temperature was raised to 100 C under which product 2a was produced in optimum
yield (93%) in 10 minutes (Table 1, entry 6). Inspired by the result, we optimized the
catalyst loading, lowering the catalyst loading to 1 mol% [Rh2(Oct)4] led to decrease
in the isolated yield (68%) (Table 1, entry 7) whereas, an increase of catalyst loading
to 3 mol%, didn’t improve yield appreciably (Table 1, entry 8). Then we have tested a
number of rhodium(II) catalysts such as, [Rh2(OPiv)4], [Rh2(S-PTTL)4],
[Rh2(S-NTTL)4], [Rh2(S-NTV)4], [Rh2(S-BNP)4] and [Rh2(OAc)4] (Table 1, entries
o
9-14) for the model reaction in toluene at 100 C. [Rh2(OPiv)4], [Rh2(S-NTTL)4] and
[Rh2(S-NTV)4] also furnished the desired pyranoindole derivative 2a in very good
yield whereas [Rh2(S-PTTL)4], [Rh2(OAc)4] and [Rh2(S-BNP)4] were found to be
comparatively less effective.
Table 1 Screening of reaction conditionsa
Entry Catalyst
Solvent
DCM
Temp.(oC) Yieldb (%)
1
2
3
4
5
6
7c
Rh2(Oct)4
Rh2(Oct)4
Rh2(Oct)4
Rh2(Oct)4
Rh2(Oct)4
Rh2(Oct)4
Rh2(Oct)4
30
30
37
51
68
78
93
68
DCE
30
Toluene
Toluene
Toluene
Toluene
Toluene
30
60
80
100
100
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8d
9
Rh2(Oct)4
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
100
100
100
100
100
100
100
91
91
46
88
81
54
14
Rh2(OPiv)4
Rh2(S-PTTL)4
Rh2(S-NTTL)4
Rh2(S-NTV)4
Rh2(OAc)4
10
11
12
13
14
Rh2(S-BNP)4
aReaction conditions: 0.2 mmol of 1a catalyzed by 2 mol%
b
Rh2L4 catalyst in 2 ml solvent for 10-30 min. Isolated yield.
cWith 1 mol% Rh2(Oct)4. dWith 3 mol% Rh2(Oct)4.
On the basis of the optimal reaction conditions (0.1 M solution of triazole in
toluene in the presence of 2.0 mol% [Rh2(Oct)4] at 100 °C), we next explored the
substrate scope as well as the functional group compatibility of our methodology
(Table 2). Electron-withdrawing substituents (R1 = Br, Cl, F) at the indole ring didn’t
influence the yield of the reactions significantly (Table 2, entries 2b-2d), in all the
cases the desired pyranoindole derivatives were achieved in good yields. While
electron-donating substituents (R1 = Me and OMe) at the indole ring led to
comparatively lower yields of the desired pyranoindoles (Table 2, entries 2e and 2f).
The intramolecular annulation of tosyl azide derived sulfonyl triazole 1h furnished the
desired pyranoindole derivative in good yield (Table 2, entry 2h). However, from the
mechanism we speculate that the electronic nature of protecting groups of indole
could have significant effect on the yield of products. Indolyl triazoles with
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electron-donating protecting groups (R2 = n-pentyl, methylcyclohexane and benzyl)
gave the desired products in good yields (Table 2, entries 2g, 2i and 2k). As expected,
protection of indole NH with electron-withdrawing group such as tosyl led to sluggish
reaction rate and lower yield (44% isolated yield, Table 2, entry 2j).
Table 2 Reaction scopea, b
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aReaction conditions: 0.2 mmol of 1, 2 mol% [Rh2(Oct)4] catalyst in 2 ml toluene at
100 oC for 10-90 min. bIsolated yield.
Indole fused seven membered rings are interesting structural motif found in
biologically active compounds and natural products.18 We also tried to explore our
protocol for the synthesis of indole fused seven membered rings. The reactions of
sulfonyl triazole 3 proceed smoothly to furnish the desired oxepinoindole 4 in 67%
isolated yield, under our optimized reaction conditions (Scheme 2a). In order to
extend the substrate scope of the method further, we tried to synthesize biologically
relevant pyridoindole derivatives. Unfortunately, the reaction of sulfonyl triazole 5
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under our optimized reaction conditions failed to give the desired pyridoindole
derivative leading to a complex mixture of undesired products (Scheme 2b).
Scheme 2. Attempted synthesis of indole lactone and pyridoindole.
Based on our previous observations,16 we envisioned that the pyranoindole
derivatives could be synthesized in one-pot starting from terminal alkynes via Cu-Rh
sequential catalysis. For that purpose, we carried out the reaction of terminal alkyne 6
with mesyl azide in the presence of CuTc (10 mol%) in toluene at room temperature.
The terminal alkyne 6 was completely converted to N-sulfonyl-1,2,3-triazole within 8
h as evident from TLC analysis. Then, the reaction mixture was added 2 mol% of
o
Rh2(Oct)4 and stirred at 100 C under nitrogen atmosphere for additional 15 min to
achieve the desired product 2a in 54% isolated yield (Scheme 3).
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Scheme 3. One-pot, sequential Cu-Rh catalyzed synthesis of pyranoindole.
A proposed mechanism of Rh(II)-catalyzed intramolecular annulation of
N-sulfonyl-1,2,3-triazoles with indole derivatives towards highly stereoselective
synthesis of pyranoindoles is outlined in Scheme 4. The N-sulfonyl-triazole 1 on
treatment with dirhodium catalyst furnishes a highly reactive rhodium(II)-azavinyl
carbene A. The intermediate A on intramolecular Friedel-Crafts alkylation results the
intermediate C, which on subsequent loss of the rhodium-catalyst and intermolecular
proton transfer from 3-position of indole ring to the nitrogen atom in enamine
generates the desired product 2 (pathway A, Scheme 4). Alternatively, intramolecular
cyclopropanation of the indole C(2)-C(3) bond gives the intermediate D (pathway B,
Scheme 4).19 The intermediate D on ring expansion and intermolecular proton transfer
from 3-position of indole ring to the enamine nitrogen atom furnishes the desired
product 2.
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Ms
N
[Rh]
R1
O
Rh2L4
1
N
R2
N2
A
N
Ms
[Rh]
N
Ms
H
pathway B
pathway A
R1
H
N
R1
F-C pathway
O
cyclopropanation
- Rh2L4
O
N
R2
R2
D
B
Ms
Ms
Ms
NH
NH
N
[Rh]
O
R1
O
H
R1
O
R1
N
R2
N
N
R2
R2
Rh2L4
C
E
2
Scheme 4. Proposed mechanism for the synthesis of pyranoindoles
3. Conclusion
In summary, an efficient rhodium(II)-catalyzed intramolecular annulation
approach towards the synthesis of pyranoindole derivatives had been demonstrated by
exploring the carbene transfer and subsequent cyclization of N-sulfonyl-1,2,3 triazole
derived Rh(II) carbenoids. A variety of pyranoindole derivatives were obtained in
moderate to excellent yields with high stereoselectivity. Moreover, a one-pot
approach for the synthesis of pyranoindole derivative was also realized starting from
terminal alkyne via sequential Cu-Rh catalysis. Further applications of this chemistry
and more detailed mechanistic investigations are underway in our laboratory.
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4. Experimental
4.1 General procedure for synthesis of triazoles 1
The N-sulfonyl-1,2,3-triazoles were synthesized from alkynes, according to a
modified version of the literature procedure.20 To a schlenk tube charged with
copper(I) thiophene-2-carboxylate (CuTC, 0.1 mmol), the alkyne (1 mmol) and
sulfonyl azide (1.1 mmol) solution in toluene were added and stirred at room
temperature. After completion (monitored by TLC), the reaction mixture was diluted
with ethyl acetate and passes through a small pad of silica. The filtrate was
concentrated and purified by column chromatography to afford the N-sulfonyl-1,2,3-
triazoles 1.
4.2 General procedure for synthesis of pyranoindoles 2
To an oven dried schlenk tube equipped with magnetic stir bar, N-sulfonyl
triazole 1 (0.2 mmol) and Rh2(Oct)4 (0.004 mmol) was added under N2 followed by
addition freshly distilled toluene (2.0 mL). The reaction was stirred at 100 °C under
N2 atmosphere and monitored with TLC analysis. After completion, the reaction
mixture was directly purified by flash column chromatography with ethyl acetate and
petroleum ether as eluents to afford 2.
4.2.1. N-((9-Methyl-2,3-dihydro-1H-carbazol-4(9H)-ylidene)methyl)methanesulf-
o
1
onamide (2a). White solid (54.5 mg, 93% yield); m.p. 147-152 C; H NMR (400
MHz, DMSO-d6) δ 9.19 (d, J = 8.1 Hz, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.47 (d, J = 8.0
Hz, 1H), 7.19 (t, J = 7.0 Hz, 1H), 7.13 (t, J = 7.0 Hz, 1H), 6.48 (d, J = 7.9 Hz, 1H),
4.90 (s, 2H), 4.46 (s, 2H), 3.61 (s, 3H), 3.08 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ 137.49, 136.00, 123.46, 121.75, 120.43, 119.83, 117.75, 112.41, 110.29, 105.45,
64.17, 62.55, 40.72, 29.90; IR (KBr plate, cm-1) νmax 519.57, 740.51, 971.00, 1086.85,
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1135.54, 1154.58, 1325.01, 1473.87, 1507.63, 1541.60, 1652.88, 3446.59; HRMS
(ESI-TOF) m/z [M+H]+, Calcd for C14H17O3N2S 293.0954. Found: 293.0954.
4.2.2. N-((6-Bromo-9-methyl-2,3-dihydro-carbazol-4(9H)-ylidene)methyl)methane-
o
1
sulfonamide (2b). White solid (57 mg, 77% yield); m.p. 174-179 C; H NMR (400
MHz, DMSO-d6) δ 9.22 (d, J = 8.3 Hz, 1H), 7.77 (s, 1H), 7.47 (d, J = 8.4 Hz, 1H),
7.30 (d, J = 8.7 Hz, 1H), 6.43 (d, J = 8.4 Hz, 1H), 4.90 (s, 2H), 4.45 (s, 2H), 3.62 (s,
3H), 3.11 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 137.48, 136.26, 124.99, 124.17,
121.83, 116.66, 113.09, 113.02, 112.37, 105.28, 64.13, 62.47, 40.95, 30.14; IR (KBr
plate, cm-1) νmax 511.02, 764.22, 788.19, 973.36, 1090.82, 1150.38, 1324.79, 1473.06,
1541.57, 3243.46, 3446.60; HRMS (ESI-TOF) m/z [M+H]+, Calcd for
C14H16O3N2BrS 371.0060. Found: 371.0059.
4.2.3. N-((6-Chloro-9-methyl-2,3-dihydro-1H-carbazol-4(9H)-ylidene)methyl)-
methanesulfonamide (2c). White solid (56 mg, 86% yield); m.p. 198-202 oC; 1H NMR
(400 MHz, DMSO-d6) δ 9.21 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 7.51 (d, J = 8.7 Hz,
1H), 7.19 (d, J = 8.3 Hz, 1H), 6.44 (d, J = 8.3 Hz, 1H), 4.89 (s, 2H), 4.45 (s, 2H), 3.62
(s, 3H), 3.12 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 137.64, 136.02, 125.04,
124.30, 121.57, 118.93, 116.71, 113.05, 111.87, 105.37, 64.13, 62.49, 40.93, 30.15;
IR (KBr plate, cm-1) νmax 516.15, 771.80, 796.49, 974.25, 1094.00, 1142.37, 1313.65,
1408.01, 1473.09, 1507.55, 1541.77, 1652.96, 3246.62; HRMS (ESI-TOF) m/z
[M+H]+, Calcd for C14H16O3N2ClS 327.0565. Found: 327.0565.
4.2.4. N-((6-Fluoro-9-methylpyrano[3,4-b]indol-4(1H,3H,9H)-ylidene)methyl)methan
o
1
-esulfonamide (2d). White solid (45.5 mg, 73% yield); m.p. 194-197 C; H NMR
(400 MHz, DMSO-d6) δ 9.17 (s, 1H), 7.49 (dd, J = 8.8, 4.5 Hz, 1H), 7.43 (d, J = 10.1
Hz, 1H), 7.03 (t, J = 9.1 Hz, 1H), 6.40 (s, 1H), 4.89 (s, 2H), 4.45 (s, 2H), 3.62 (s, 3H),
13
3.11 (s, 3H); C NMR (100 MHz, DMSO-d6) δ 158.03, 137.87, 134.20, 123.38,
117.33, 112.67, 111.31, 109.46, 105.65, 105.01, 64.18, 62.55, 40.78, 30.17; IR (KBr
13

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plate, cm-1) νmax 519.07, 775.28, 790.73, 844.75, 898.33, 926.53, 980.45, 1084.63,
1146.36, 1316.31, 1403.47, 1488.84, 1542.87, 1622.15, 3269.29; HRMS (ESI-TOF)
m/z [M+H]+, Calcd for C14H16O3N2FS 311.0860. Found: 311.0857.
4.2.5. N-((6,9-Dimethyl-2,3-dihydro-1H-carbazol-4-ylidene)methyl)methane-
o
sulfonamide (2e). White solid (45.6 mg, 71% yield); m.p. 168-172 C; 1H NMR (400
MHz, DMSO-d6) δ 9.12 (d, J = 8.5 Hz, 1H), 7.42 (s, 1H), 7.35 (d, J = 8.3 Hz, 1H),
7.01 (d, J = 8.2 Hz, 1H), 6.44 (d, J = 8.5 Hz, 1H), 4.88 (s, 2H), 4.45 (s, 2H), 3.58 (s,
3H), 3.08 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 136.10, 135.96,
129.07, 123.72, 123.20, 119.62, 118.45, 112.09, 109.98, 104.93, 64.22, 62.58, 40.71,
29.91, 21.78; IR (KBr plate, cm-1) νmax 517.49, 766.08, 797.86, 971.87, 1091.63,
1140.76, 1315.74, 1408.90, 1490.44, 1542.28, 3267.00; HRMS (ESI-TOF) m/z
[M+H]+, Calcd for C15H19O3N2S 307.1111. Found: 307.1108.
4.2.6. N-((6-methoxy-9-methylpyrano[3,4-b]indol-4-ylidene)methyl)
methanesulfonamide (2f) White solid, 42.5 mg, 66% yield. m.p. 155-156 oC; 1H NMR
(400 MHz, DMSO) δ 9.13 (d, J = 8.5 Hz, 1H), 7.39 (d, J = 8.9 Hz, 1H), 7.08 (d, J =
1.6 Hz, 1H), 6.86 (dd, J = 8.8, 1.7 Hz, 1H), 6.39 (d, J = 8.5 Hz, 1H), 4.88 (s, 2H),
13
4.45 (s, 2H), 3.80 (s, 3H), 3.59 (s, 3H), 3.08 (s, 3H); C NMR (101 MHz, DMSO) δ
154.55, 136.71, 132.80, 123.81, 118.41, 112.02, 110.91, 110.36, 105.01, 103.18,
64.23, 62.62, 56.00, 40.69, 30.02; IR (KBr plate, cm-1) νmax 798.56, 973.21, 1090.40,
1159.65, 1235.83, 1317.78, 1491.14, 1616.95, 3158.56; HRMS (ESI-TOF) m/z
[M+H]+, Calcd for C15H19O4N2S 323.1057. Found: 323.1060.
4.2.7. N-((9-Pentylpyrano[3,4-b]indol-4(1H,3H,9H)-ylidene)methyl)methane-
o
1
sulfonamide (2g). White solid (51.7 mg,74% yield); m.p. 145-149 C; H NMR (400
MHz, DMSO-d6) δ 9.17 (d, J = 8.6 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.48 (d, J = 8.0
Hz, 1H), 7.15 (dt, J = 14.7, 7.1 Hz, 2H), 6.49 (d, J = 8.5 Hz, 1H), 4.89 (s, 2H), 4.47
(s, 2H), 4.04 (t, J = 6.9 Hz, 2H), 3.08 (s, 3H), 1.69 – 1.45 (m, 2H), 1.37 – 1.11 (m,
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4H), 0.83 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 136.84, 135.58,
123.56, 121.78, 120.39, 119.94, 117.80, 112.46, 110.53, 105.54, 64.28, 62.63, 43.25,
40.73, 29.84, 28.85, 22.29, 14.32; IR (KBr plate, cm-1) νmax 418.91, 742.08, 801.67,
1093.27, 1144.74, 1323.08, 1419.49, 1457.54, 1473.89, 1507.51, 1540.68, 1558.31,
1636.08, 2927.88, 3241.10, 3446.21; HRMS (ESI-TOF) m/z [M+H]+, Calcd for
C18H25O3N2S 349.1580. Found: 349.1575.
4.2.8. 4-methyl-N-((9-methylpyrano[3,4-b]indol-4(1H,3H,9H)-ylidene)methyl)-
o
1
benzenesulfonamide (2h) White solid, 65.5 mg, 89% yield. m.p. 91-94 C; H NMR
(400 MHz, DMSO) δ 9.67 (d, J = 8.9 Hz, 1H), 7.76 (d, J = 6.9 Hz, 2H), 7.59 – 7.27
(m, 3H), 7.17 (dd, J = 17.8, 7.9 Hz, 2H), 6.38 (d, J = 8.7 Hz, 1H), 5.77 (s, 1H), 4.84
(s, 2H), 4.33 (s, 2H), 3.58 (s, 3H), 2.36 (s, 3H); 13C NMR (101 MHz, DMSO) δ
143.54, 138.11, 137.44, 136.21, 130.28, 126.72, 123.31, 121.76, 120.63, 119.38,
118.69, 111.68, 110.40, 105.15, 63.98, 62.45, 55.39, 29.89; IR (KBr plate, cm-1) νmax
550.91, 1050.42, 1085.33, 1138.44, 1159.58, 1326.95, 1474.06, 2973.13, 3420.69;
HRMS (ESI-TOF) m/z [M+H]+, Calcd for C20H21O3N2S 369.1265. Found: 369.1267.
4.2.9. N-((9-(Cyclohexylmethyl)pyrano[3,4-b]indol-4(1H,3H,9H)-ylidene)methyl)-
methane-sulfonamide (2i). White solid (61.5 mg, 82% yield); m.p. 94-97 oC; 1H NMR
(400 MHz, CD2Cl2) δ 7.62 (d, J = 7.8 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.13 (t, J =
7.4 Hz, 1H), 7.07 (t, J = 7.3 Hz, 1H), 6.48 (d, J = 8.3 Hz, 1H), 6.26 (d, J = 8.2 Hz,
1H), 4.78 (s, 2H), 4.44 (s, 2H), 3.67 (d, J = 7.4 Hz, 2H), 2.97 (s, 3H), 1.75 – 1.65 (m,
2H), 1.60 – 1.48 (m, 4H), 1.08 (s, 3H), 0.96 – 0.77 (m, 2H); 13C NMR (100 MHz,
CD2Cl2) δ 137.27, 135.82, 123.62, 121.75, 121.68, 120.34, 119.87, 110.44, 110.18,
105.07, 64.19, 63.20, 53.85, 50.14, 40.17, 38.69, 31.07, 31.03, 26.24, 25.74; IR (KBr
plate, cm-1) νmax 481.49, 742.26, 801.56, 977.01, 1093.63, 1145.37, 1323.25, 1419.59,
1457.74, 1507.49, 1540.76, 1636.17, 2927.71, 3241.54; HRMS (ESI-TOF) m/z
[M+H]+, Calcd for C20H27O3N2S 375.1737. Found: 375.1730.
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4.2.10. N-((9-Tosylpyrano[3,4-b]indol-4(1H,3H,9H)-ylidene)methyl)methane-
o
1
sulfonamide (2j). White solid (38.1 mg, 44% yield); m.p. 64-69 C; H NMR (400
MHz, DMSO-d6) δ 9.68 (d, J = 8.8 Hz, 1H), 8.06 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.3
Hz, 2H), 7.69 (d, J = 7.1 Hz, 1H), 7.44 – 7.27 (m, 4H), 6.72 (d, J = 8.6 Hz, 1H), 5.12
(s, 2H), 4.45 (s, 2H), 3.14 (s, 3H), 2.31 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ
146.22, 135.79, 134.19, 133.04, 130.83, 127.05, 126.62, 125.35, 124.92, 120.79,
118.07, 115.10, 114.50, 111.90, 64.35, 63.31, 41.42, 21.49; IR (KBr plate, cm-1) νmax
518.85, 580.42, 666.07, 748.72, 858.73, 973.71, 1090.13, 1151.83, 1250.83, 1348.89,
1451.75, 1645.46, 2925.79; HRMS (ESI-TOF) m/z [M+H]+, Calcd for C20H21O5N2S2
433.0886. Found: 433.0888.
4.2.11. N-((9-Benzylpyrano[3,4-b]indol-4(1H,3H,9H)-ylidene)methyl)methane-
sulfonamide (2k). White solid (53.8 mg, 73% yield); m.p. 177-178 oC; 1H NMR (400
MHz, DMSO-d6) δ 9.22 (d, J = 8.7 Hz, 1H), 7.69 (d, J = 6.5 Hz, 1H), 7.51 (d, J = 7.1
Hz, 1H), 7.30 (t, J = 7.0 Hz, 2H), 7.25 (d, J = 6.5 Hz, 1H), 7.19 – 7.11 (m, 2H), 7.06
(d, J = 7.1 Hz, 2H), 6.54 (d, J = 8.6 Hz, 1H), 5.35 (s, 2H), 4.83 (s, 2H), 4.47 (s, 2H),
13
3.09 (s, 3H); C NMR (100 MHz, DMSO-d6) δ 138.15, 137.18, 135.67, 129.18,
127.85, 126.95, 123.68, 122.09, 120.72, 120.03, 117.26, 112.94, 110.83, 106.23,
64.27, 62.72, 60.24, 46.56, 21.23, 14.56; IR (KBr plate, cm-1) νmax 519.44, 737.77,
976.03, 1094.91, 1137.75, 1322.36, 1457.01, 1541.47, 1652.76, 3259.95; HRMS
(ESI-TOF) m/z [M+H]+, Calcd for C20H21O3N2S 369.1267. Found: 369.1263.
4.2.12. N-((10-Methyl-1-oxo-3,4-dihydro-1H-oxepino[3,4-b]indol-5(10H)-ylidene)
o
methyl)methane-sulfonamide (2l). White solid (39.1 mg, 61% yield); m.p. 83-87 C;
1H NMR (400 MHz, DMSO-d6) δ 9.27 (s, 1H), 8.31 (d, J = 7.7 Hz, 1H), 7.69 (d, J =
8.1 Hz, 1H), 7.38 (dt, J = 14.7, 7.1 Hz, 2H), 5.78 (s, 1H), 4.68 – 4.52 (m, 1H), 4.31
(dd, J = 16.8, 9.3 Hz, 1H), 3.85 (s, 3H), 3.15 (s, 3H), 3.01 (dt, J = 19.5, 9.9 Hz, 1H),
13
2.89 – 2.67 (m, 1H); C NMR (100 MHz, DMSO-d6) δ 211.59, 163.85, 145.53,
138.50, 124.97, 124.93, 123.88, 122.54, 111.65, 111.10, 75.19, 65.59, 40.87, 36.54,
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32.30; IR (KBr plate, cm-1) νmax 512.69, 785.44, 965.35, 1138.49, 1299.74, 1473.38,
1558.97, 1716.58, 2925.76, 3446.42; HRMS (ESI-TOF) m/z [M+H]+, Calcd for
C15H17O4N2S 321.0904. Found: 321.0899.
4.3 One-pot synthesis of pyranoindole starting from alkyne
To an oven dried schlenk tube charged with alkyne (0.2 mmol) and CuTC (0.02
mmol) in toluene, was added mesyl azide (0.2 mmol) and stirred at room temperature.
After 8 h alkyne was completed converted to the corresponding N-sulfonyl triazole
and Rh2(Oct)4 (0.004 mmol) was added and stirred at 100 °C. After completion, the
reaction mixture was directly purified by flash column chromatography with ethyl
acetate and petroleum ether as eluents to achieve the desired pyranoindole derivative
2a (31.5 mg, 54% yield).
Acknowledgements
We thank Prof. Daqiang Yuan (Fujian Institute of Research on the Structure of Matter,
Chinese Academy of Sciences) for his kind help in an X-ray analysis. This work was
supported by the National Natural Science Foundation of China (21302183), the
"Strategic Priority Research Program" of the Chinese Academy of Sciences (Grant No.
XDA09030102), China Postdoctoral Science Foundation (Grant No. 2015M571975)
and 100 Talents Programme of the Chinese Academy of Sciences.
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